Automated Positive Pressure Solid Phase Extraction Apparatus and Method

ABSTRACT

An automated positive pressure solid phase extraction apparatus and method comprising two tiered lifts devices each individually controllable to individually vertically translate within an elevator framework between a base on which the elevator framework is mounted and a manifold plate supported by the framework in a substantially horizontal plane parallel with and vertically above the two tiered lifts devices and a rectilinearly translating shuttle assembly comprising a shuttle supporting labware for rectilinear travel into and out of the elevator framework to handoff the labware to one of the two tiered elevator lifts or both.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of, and claims the benefitof priority under 35 U.S.C. §§120 and 121 to, U.S. application Ser. No.14/598,876, filed Jan. 16, 2015, currently pending and which is herebyincorporated by reference herein in its entirety and which claimspriority under 35 USC Section 119(e) to U.S. Provisional PatentApplication No. 61/928,873, filed Jan. 17, 2014, the disclosure of whichis incorporated herein by reference in its entirety.

FIELD OF THE INVENTION

This invention relates generally to a positive pressure solid phaseextraction apparatus and method and, in particular, to an automatedpositive pressure solid phase extraction apparatus and method havingstand-alone utilization and utilization with, for example, an automatedmaterial handling system such as an automated pipetting workstation.

BACKGROUND OF THE INVENTION

Currently, the separation of compounds in a solid phase extraction (SPE)process is accomplished by vacuum and positive pressure methodologies.While automated systems exist for use with vacuum, the weakness is inthat the application of vacuum is across the whole filter plate. This isbecause as media is pulled through a filter, the resultingcompound/component cannot come into contact with anything except thewell that is intended to catch the compound to eliminate potential crosscontamination. For a filter plate that contains an array of wells(currently up to 384) the vacuum applied to an individual well in thearray is not equal to any other well due to the resistance differencesof the wells in the array as the media is filtered. Some wells in thearray will pass the media through the filter faster than others and whenthey have completely passed the media, those wells become even lessrestrictive and thus allow more air to flow through subsequentlyreducing the amount of air flowing through the remaining wells. As aresult, it is difficult to guarantee all wells have filtered their mediawithin a given time allotment.

An additional weakness of currently known vacuum based devices is thatuser interaction is required in the selection and/or adjustment ofadapters to set the height between the filter plate and the collectionor micro plate for the purpose of engaging the nozzles of the filterplate into the wells of the collection or micro plate. The engagement isnecessary to prevent possibility of cross contamination across wells.This manual process can be iterative requiring time and can be furtherproblematic in determining the correct engagement to prevent crosscontamination.

Examples of these vacuum based SPE devices are the AVS on the ML4000 andML STAR, the CVS on the ML STAR, and the NVS on the ML Nimbus. All ofthese instrumentalities and systems are manufactured and sold by theassignee of the present patent application, Hamilton Company, 4970Energy Way, Reno, Nev. 89502, United States Of America.

Positive Pressure is a solution to the problem of even flow distributionas flow restrictors can be employed to guarantee even distribution ofpressure and flow to individual wells. Flow restrictors per well cannotbe employed on a vacuum system as they would come into contact with theliquids being processed creating the potential for contamination. Whilethere are positive pressure apparatus currently available, the weaknessof those devices is that they are not, inter alia, friendly to automatedpipetting workstations and require user interaction at virtually everystage of the SPE process as a stand-alone unit.

Hence, there is a need to overcome the significant shortcomings of theknown prior-art as delineated hereinabove.

BRIEF SUMMARY OF THE INVENTION

Accordingly, and in one aspect, an embodiment of the inventionameliorates or overcomes one or more of the shortcomings of the knownprior art by providing a positive pressure solid phase extraction (SPE)apparatus comprising a shuttle assembly having a shuttle reciprocallymovable along a longitudinal length of a base plate on which the shuttleassembly is mounted; a tiered elevator lift assembly disposed on thebase plate and vertically extending therefrom so as to partition thelongitudinal length of the base plate into an accessible home position(e.g., a gripper and pipetter/probe head assembly accessible homeposition) and an inaccessible away position under a vertically elevatedmanifold plate for presenting labware from the shuttle to an upperand/or lower tiered lift device of the tiered elevator assembly locatedbelow the manifold plate wherein the upper and lower tiered lift devicesand the shuttle are individually controllable to shuttle labware intothe elevator assembly and present it to the upper and lower lifts of thetiered elevator lift mechanism having vertically controllable liftheights of one labware piece or two tiered labware pieces up to amanifold plate positioned vertically above the upper and lower tieredlift devices so as to allow controlled settings of the height betweentwo tiered labware pieces being presented to the manifold plate suchthat in one aspect cross contamination is precluded such as isexemplified when the tiered labware being presented to the manifold is afilter plate surmounting a collection at the controlled heighttherebetween.

In another aspect, an embodiment of the invention provides an automatedpositive pressure SPE apparatus that is presented to an accessiblelocation on an automated pipetting workstation. The automated pipettingworkstation interacts with the automated positive pressure SPE apparatusby placing labware on and removing labware from a shuttle of a shuttleassembly of the apparatus that is reciprocally movable along alongitudinal length of a base plate on which the shuttle assembly ismounted. Additionally, the pipetting workstation dispenses liquids tothe labware as needed during the SPE process. Furthermore, the positivepressure SPE apparatus comprises a tiered elevator lift assembly mountedon the base plate and vertically extending therefrom such that thelongitudinal length of travel of the shuttle along the base plate allowsthe shuttle to reciprocate in and out of the tiered elevator liftassembly for presenting labware to an upper tiered lift device and alower tiered lift device of the tiered elevator lift assembly such that,after the interaction with the automated pipetting workstation, theapparatus shuttles the labware into the tiered elevator lift assemblyand presents the labware to the upper and lower tiered lift devices thatare independently driven to present the labware such as a filter plateto a positive pressure manifold disposed in a horizontal planevertically above and substantially parallel to the upper and lowertiered lift devices wherein a user specified and software controlledpressure is applied to the filter plate via the positive pressuremanifold for a user specified and software controlled time period forthe purpose of separating liquid compounds into their individualcomponents of interest. The tiered elevator lift assembly can furtherprovide simultaneous or sequential vertical lifting of a collection orwaste plate below the filter plate. Additionally, and in one aspect, thetiered elevator lift assembly is software controlled to providepositioning of the filter plate and collection plate to engage thenozzles of the filter plate into the wells of the collection plate viasoftware labware definitions eliminating the need for user interactionfor adjustment. This further allows for multiple combinations of filterand collection plates to be used without user interaction foradjustment.

In another aspect, an embodiment of the invention provides an automatedpositive pressure SPE apparatus comprising a process security system forproviding process security by use of pressure and temperature sensorsthat monitor the pressure and temperature change over time for an arrayof wells, for example up to 96, during the SPE process. The use of thepressure sensors provides process security for each well of the labwareby collecting pressure data which the process security system utilizesto construct a curve of the process. This curve is then compared by theprocess security system to a previously stored standard acceptable curvewith tolerance boundaries defined from which a pass/error decision ismade by the process security system regarding the completeness andtimeliness of the process being measured. Errors are presented to theuser and recorded permanently in a log file with time and date fortraceability. The temperature sensors provide additional processsecurity in applications that are sensitive to temperature variances byrecording the temperature of each well in the labware at various timesduring the process and having, for example, a bench mark to which therecorded temperatures are compared to for making pass/error decision.Temperature values are also recorded permanently in a log file with dateand time for traceability and future use.

In another aspect, an embodiment of the invention provides an automatedpositive pressure SPE apparatus that serves as an evaporator fordownstream SPE processes by placing an evaporator adapter onto theshuttle assembly which presents the adapter to the upper tiered liftdevice. The upper tiered lift device presents the evaporator adapter tothe manifold plate through which the apparatus controls both the flowand heat added via a heater control unit to the system air.Subsequently, this air flows through the evaporator adapter into labwarewhich is presented to the adapter by the lower tiered lift device. Thelabware is presented in close proximity to the evaporator adapter suchthat the controlled heated air is directed onto the liquid surface to beevaporated without the adapter being in direct contact with the liquidbeing evaporated. Evaporated vapors are directed through a plenum to aduct which is connected to the user's ventilation system. During theevaporation process, the lower tiered lift device moves to keep theliquid being evaporated in close proximity to the evaporator adapter tomaximize efficiency of the evaporation process.

In another aspect, an embodiment of the invention provides an automatedpositive pressure SPE apparatus that serves as a tip dryer by means ofpresenting a rack of tips to the upper tiered lift device by the shuttleassembly. The upper tiered lift device presents the rack of tips to themanifold plate through which the apparatus controls the flow ofcontrolled heated air. Subsequently, this air flows through theindividual tips and any liquid is captured by the shuttle assembly anddirected to a liquid waste container.

In another aspect, an embodiment of the invention provides an automatedpositive pressure SPE apparatus that serves as a cap mat sealing device.First, labware is placed on the shuttle assembly. Then a cap mat isplaced onto the top of the labware. The shuttle assembly presents thestack to the upper tiered lift device. The upper tiered lift devicepresents the stack to the manifold plate and applies force as ifattempting to seal the labware against the manifold plate in the SPEprocess. This will seat the cap mat into the labware. Air pressure canbe additionally applied to further seat the cap mat into the labware tocreate the necessary seal.

Further advantages of the automated positive pressure SPE apparatus andmethod will become apparent from the detailed description providedbelow, when taken together with the attached drawings and claims. Itshould be understood, however, that numerous modifications andadaptations may be resorted to without departing from the scope and fairmeaning of the claims as set forth hereinbelow following the detaileddescription of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a forward lateral end and front longitudinal side perspectiveview of an embodiment of an automated positive pressure solid phaseextraction (SPE) apparatus with lateral side plates removed therefrom.

FIG. 2 is a perspective view illustrating the automated positivepressure SPE apparatus disposed on a rear lateral deck portion of anembodiment of an automated pipetting workstation, the workstation havinga gripper and pipetter/probe head assembly operatively coupled to arobotic gantry and the view further illustrating a computer operativelycoupled to the workstation and the automated positive pressure SPEapparatus, and the view further illustrating a manifold pressure sourceassembly and a waste assembly operatively coupled to the automatedpositive pressure SPE apparatus.

FIG. 3 is a general block diagram view of the automated positivepressure SPE apparatus shown operatively coupled to the automatedpipetting workstation, both of which are operatively coupled to acomputer/controller that can be connected to an optional LAN or server.

FIG. 4 is an exploded parts perspective view detailing a base plate, ashuttle assembly, a manifold framework assembly, and a vertical guiderail assembly of the automated positive pressure SPE apparatus.

FIG. 5 is a partial exploded parts perspective view detailing parts ofthe shuttle assembly and a lower tiered lift device.

FIG. 6 is a bottom plan view detailing the shuttle assembly and thelower tiered lift device of the automated positive pressure SPEapparatus.

FIG. 7 is a partial exploded parts perspective view detailing anelevated manifold assembly and PCB housing and PCB controller and aperspective view of the shuttle assembly, and a tiered elevator liftassembly of the automated positive pressure SPE apparatus.

FIG. 8 is a partial exploded parts perspective view detailing an uppertiered lift device and a perspective view illustrating details of theshuttle assembly and the lower lift device of the automated positivepressure SPE apparatus.

FIG. 9 is a top front longitudinal view detailing the shuttle assemblyincluding a waste tray or trough, the manifold framework assembly, thevertical guide rail assembly, and the tiered elevator lift assembly ofthe automated positive pressure SPE apparatus.

FIG. 10 is a top plan view detailing the shuttle assembly including thewaste tray, the manifold framework assembly, the vertical guide railassembly, and the tiered elevator lift assembly of the automatedpositive pressure SPE apparatus.

FIG. 11 is a forward lateral end and rear longitudinal side perspectiveview of the automated positive pressure SPE apparatus illustratedfurther with a pair of forward and a pair of rearward longitudinal sideplates.

FIG. 12 is a general flow chart of an embodiment of an automatedpositive pressure SPE sequencing process of the automated positivepressure SPE apparatus.

FIG. 13 is a further detailed flow diagram of the automated positivepressure SPE sequencing process of the automated positive pressure SPEapparatus charted in FIG. 12.

FIG. 14 is a front plan view of the automated positive pressure SPEapparatus shown in an initialized state.

FIG. 15 is a front plan view of the automated positive pressure SPEapparatus shown receiving labware in the form of a filter plate from thegripper of the automated pipetting workstation wherein the filter plateis tiered above and mates with the waste tray that is mounted on theshuttle assembly located at an accessible position of the gripper andpipetter or probe head assembly of the automated pipetting workstationfor locating the filter plate and performing a conditioning stepcomprising dispensing a conditioning agent into the filter plate at theaccessible position while capturing all fluids which are pushed throughthe filter plate in the conditioning step.

FIG. 16 is a front plan view of the automated positive pressure SPEapparatus shown with the shuttle assembly transported within theelevated manifold assembly and the filter plate positioned via sensorsover locating pins of the upper elevator device to ensure positionalaccuracy while the filter plate is being lifted up to engage themanifold while simultaneously presenting the waste tray over locatingpins of the lower elevator device to ensure positional accuracy whilethe waste tray is being lifted up to engage under the filter plateengaged under the manifold plate.

FIG. 17 is a front plan view of the automated positive pressure SPEapparatus shown presenting the filter plate to the manifold plate withthe upper elevator and positioning the waste tray with the lowerelevator during the conditioning phase.

FIG. 18 is a front plan view of the automated positive pressure SPEapparatus shown with the filter plate repositioned back to the automatedpipetting workstation accessible position and the elevator assembliesdown with the condition process completed to allow the pipetter todispense the sample to be separated into the filter plate.

FIG. 19 is a front plan view of the automated positive pressure SPEapparatus shown with the shuttle assembly transported back within theelevated manifold assembly and the filter plate positioned via sensorsover locating pins of the upper elevator device to ensure positionalaccuracy while the filter plate is being lifted up to engage themanifold while simultaneously presenting the waste tray over locatingpins of the lower elevator device to ensure positional accuracy whilethe waste tray is being lifted up to engage under the filter plateengaged under the manifold plate.

FIG. 20 is a front plan view of the automated positive pressure SPEapparatus shown presenting the filter plate with the sample therein tothe manifold with the upper elevator and positioning the waste troughwith the lower elevator during the sample addition phase.

FIG. 21 is a front plan view of the automated positive pressure SPEapparatus shown with the filter plate repositioned back to the automatedpipetting workstation accessible position and the elevator assembliesdown to allow the pipetter to dispense the washing agent into the filterplate.

FIG. 22 is a front plan view of the automated positive pressure SPEapparatus shown with the shuttle assembly transported back within theelevated manifold assembly and the filter plate with the washing agentpositioned via sensors over locating pins of the upper elevator deviceto ensure positional accuracy while the filter plate is being lifted upto engage the manifold plate while simultaneously presenting the wastetray over locating pins of the lower elevator device to ensurepositional accuracy while the waste tray is being lifted up to engageunder the filter plate engaged under the manifold plate.

FIG. 23 is a front plan view of the automated positive pressure SPEapparatus shown presenting the filter plate with the washing agenttherein to the manifold with the upper elevator and positioning thewaste trough with the lower elevator during the washing phase.

FIG. 24 is a front plan view of the automated positive pressure SPEapparatus shown with the lower elevator at the at home position, theshuttle assembly with the waste tray repositioned back to the automatedpipetting workstation accessible position or the shuttle assembly hometo allow the pipetter to place the collection plate on the shuttleassembly while the upper elevator device maintains the vertical abutmentof the filter plate, with the remaining sample therein, below themanifold plate.

FIG. 25 is a front plan view of the automated positive pressure SPEapparatus shown with the collection plate transported within theelevated manifold assembly and positioned via sensors over locating pinsof the lower elevator device to ensure positional accuracy while thecollection plate is being lifted up to engage under the filter plateengaged under the manifold plate to allow the upper elevator device tolower the filter plate onto the collection plate.

FIG. 26 is a front plan view of the automated positive pressure SPEapparatus shown with the elevator assemblies in relatively downpositions with the shuttle assembly transported back to the automatedpipetting workstation accessible position with both the collection plateand filter plate thereon to allow the pipetter to dispense an elutionagent to the filter plate.

FIG. 27 is a front plan view of the automated positive pressure SPEapparatus shown with the shuttle assembly and both the collection plateand filter plate with the elution agent disposed thereon transportedwithin the elevated manifold assembly with the filter plate with theelution agent positioned via sensors over locating pins of the upperelevator device to ensure positional accuracy while the filter plate isbeing lifted up to engage the manifold plate while simultaneouslypresenting the collection plate over locating pins of the lower elevatordevice to ensure positional accuracy while the collection plate is beinglifted up to engage the nozzles on the filter plate which, in turn, isengaged under the manifold plate.

FIG. 28 is a front plan view of the automated positive pressure SPEapparatus shown with the filter plate with the elution agent thereinengaged with the manifold by the upper elevator and further shown withthe collection plate engaged with the filter plate wherein the nozzlesof the filter plate aligned with wells of the collection plate topreclude cross-contamination.

FIG. 29 is a front plan view of the automated positive pressure SPEapparatus shown with the collection plate shuttled back to the automatedpipetting workstation accessible position to allow the pipetter toremove the collection plate from the shuttle.

FIG. 30 is a front plan view of the automated positive pressure solidphase extraction apparatus shown presenting the filter plate back to theautomated pipetting workstation accessible position to allow thepipetter to remove the filter plate from the shuttle.

FIG. 31 is a perspective view illustrating a plurality of the automatedpositive pressure SPE apparatuses disposed on a rear lateral deckportion of another embodiment of an automated pipetting workstation onlyframework of which is illustrated for clarity of illustration of eachSPE apparatus disposed on the deck.

FIG. 32 is a perspective view illustrating the automated positivepressure SPE apparatus disposed on an automated pipetting workstation,the workstation having a gripper and pipetter/probe head assemblyoperatively coupled to a robotic gantry and the view furtherillustrating a computer operatively coupled to the workstation and theautomated positive pressure SPE apparatus, and the view furtherillustrating a heater control unit, the manifold pressure sourceassembly, and the waste assembly operatively coupled to the automatedpositive pressure SPE apparatus.

FIG. 33 is a general flow diagram of an embodiment of an automatedpositive pressure SPE sequencing process of the automated positivepressure SPE apparatus further comprising an evaporation process.

FIG. 34 is a further detailed flow diagram of the evaporation process.

FIG. 35 is a front plan view of the automated positive pressure SPEapparatus shown receiving an evaporator adapter from the automatedpipetting workstation during the evaporation process.

FIG. 36 is a front plan view of the automated positive pressure SPEapparatus shown presenting the evaporator adapter to the manifold withthe upper elevator during the evaporation process.

FIG. 37 is a front plan view of the automated positive pressure SPEapparatus shown presenting the shuttle assembly back to the automatedpipetting workstation accessible position to allow the automatedpipetting workstation to place the collection plate on the shuttle.

FIG. 38 is a front plan view of the automated positive pressure SPEapparatus shown presenting the shuttle assembly with the collectionplate back to the lower elevator which will lift the collection plate toengage the needles of the evaporator adapter.

FIG. 39 is a front plan view of the automated positive pressure SPEapparatus shown with both the evaporator adapter and collection plateengaged.

FIG. 40 is an exploded parts perspective view detailing a heatermanifold assembly of the automated positive pressure SPE apparatus, theheater manifold assembly comprising a heater manifold unit housing aheater PCB and a plenum operatively coupled to a duct which is connectedto the user's ventilation system.

FIG. 41 is a front plan view of the automated positive pressure SPEapparatus shown presenting the collection plate back to the automatedpipetting workstation accessible position to allow the automatedpipetting workstation to remove the collection plate from the shuttle.

FIG. 42 is a front plan view of the automated positive pressure SPEapparatus shown presenting the evaporator adapter back to the automatedpipetting workstation accessible position to allow the automatedpipetting workstation to remove the evaporator adapter from the shuttle.

FIG. 43 is an electrical block diagram view of an embodiment of theautomated positive pressure SPE system comprising a process securitysystem comprised of pressure and temperature monitoring systems.

FIG. 44 is a forward lateral end and front longitudinal side perspectiveview of an embodiment of the positive pressure solid phase extraction(SPE) mechanism with lateral side plates removed there from forillustrating an elevator outboard location of the top elevator tierdrive motor.

FIG. 45 is a top rear longitudinal view detailing the elevator outboardlocation of the top elevator tier drive, the bottom tier drive, theshuttle drive, and the tiered elevator lifts of the automated positivepressure SPE apparatus.

FIG. 46 is a top rear longitudinal partial exploded parts view furtherdetailing a upper tiered lift belt assembly for the top elevator tierdrive.

DETAILED DESCRIPTION OF THE INVENTION

Considering the drawings, wherein like reference numerals denote likeparts throughout the various drawing figures, reference numeral 10 isdirected to an embodiment of an automated positive pressure solid phaseextraction (SPE) apparatus and reference 410 (FIG. 3) is directed to apositive pressure solid phase extraction system formed by the positivepressure solid phase extraction apparatus 10 and associated methoddescribed below in combination with an automated material handlingsystem in the form of, but not limited to an automated pipettingworkstation 420.

Referring to FIG. 1, and in its essence, apparatus 10 comprises a baseplate 20; a shuttle assembly 44 comprising a shuttle 60; an elevatedmanifold assembly 110 comprising a manifold framework assembly 112 and amanifold plate assembly 160; a waste tray assembly comprising a wastetray 580; and a tiered elevator lift assembly 192 comprising a lowertiered lift device 230 and an upper tiered lift device 280.

FIG. 2 illustrates an embodiment of the positive pressure SPE apparatus10 disposed on a posterior portion of a deck 422 of the automatedpipetting workstation 420. As also illustrated, the positive pressureSPE apparatus 10 is operatively coupled to a waste assembly 560, amanifold pressure source assembly 550, and a computer 520 that is alsooperatively coupled to workstation 420. As illustrated in FIG. 32, thepositive pressure SPE apparatus 10 is further operatively coupled to aheater control unit 700.

Workstation

Referring to FIG. 2, and in one embodiment, the automated pipettingworkstation 420 comprises a robotic gantry 430 operatively carrying,vertically above workstation deck 422, both a multi-channel pipettingassembly 440 having a multi-channel pipetting head 442 and a labwaregripper arm assembly 450 having engaging fingers 452.

Robotic gantry 430 provides three degrees of freedom that includelongitudinal translation along the direction of the double ended arrow“X”, latitudinal translation along the double ended arrow “Y” andvertical translation along the double ended arrow “Z” so that thepipetting head 442 and the engaging fingers 452 can move along thelength and width of the deck 422 and vertically up and down relativethereto. Additionally, the labware gripper arm assembly 450 provides theengaging fingers 452 with the ability to rotate about the double endedarrow “W” and to provide telescopic extension. The engaging fingers 452grasp side edges of labware to be described.

In general, and as conventional in the art and informed by the instantdisclosure, a fluid delivery system provides a controlled delivery offluid within the multi-channel pipetting head 442 comprising amultiplicity of individual probe tips each of which can carry same ordifferent fluids as dictated by the system setup. In one embodiment, themulti-channel pipetting head 442 comprises 96 tips oriented in an 8x12array. Other probe arrays and tip populations are possible.

In one embodiment, the control of the multi-channel pipetting head 442is controlled by the computer 520 which can also control the roboticgantry 430 and the positive pressure SPE apparatus 10 and its sequencingprotocols.

Controller

Referring now to FIGS. 1 through 3, and in one embodiment, the positivepressure SPE apparatus 10 comprises a controller 400 laid out on aprinted circuit board (PCB) thereby defining a controller PCB 400 thatattaches to a rear or posterior latitudinal plate 172 via standoffs andscrews as further illustrated in FIG. 7.

The controller 400 is operatively coupled to both the automatedpipetting workstation 420 and computer/controller 520 for providingcommunication therewith for controlling the tiered elevator liftassembly 192 and the shuttle assembly 44.

Additionally, and in one embodiment, the controller 400 is operativelycoupled to four sensors such as optical interrupt switches 102, 104;402, and 404.

Referring to FIGS. 3 and 4, and in one embodiment, sensors 102, 104provide an indication of one of two positions or states of the shuttle60 having corresponding sensor target, trip, or flag member 98 mountedon the side of the shuttle 60 as delineated below. Sensor 402 providesan indication of a defined lower home position of the lower lift device230 having corresponding sensor target, trip, or flag member 406 (FIG.5) mounted on and interiorly downwardly depending from support member234 of forked lower lift member 232. Similarly, sensor 404 provides anindication of a defined lower home position of the upper lift device 280having corresponding sensor target, trip, or flag member 408 (FIG. 10)mounted on and interiorly downwardly depending from support member 286(FIG. 8) of forked upper lift member 282. The controller 400 cancommunicate sensor information to the computer/controller 520 andworkstation 420.

Furthermore, power supply 570 provides power to the positive pressureSPE apparatus 10 and to controller 400. The automated pipettingworkstation 420 receives power from power supply 572.

As noted above, the computer/controller 520 can also provide control ofthe automated pipetting workstation 420 via a main controller 454 andPipetto axis controller 456. As was also noted above, thecomputer/controller 520 can also provide control of the manifoldcontrolled pressure source assembly 550 and waste assembly 560. Thecomputer/controller 520 can also provide control of the heater controlunit 700.

Moreover, computer/controller 520 comprises storage memory 528 whichcomprises a non-transitory computer readable medium 530 having anoperating system 532 and software 534 stored thereby. User defined SPEprocesses 536 for the positive pressure solid phase extraction apparatus10 may also be stored in the non-transitory computer readable medium530. Computer/controller 520 may be operatively couple to optional LANand/or server 538.

Base Plate

Now referring to FIG. 4, and in one embodiment, the apparatus 10comprises base plate 20 having a central longitudinal axis 22 that isalso the central longitudinal axis of the apparatus 10. The base plate20 comprises forward and rearward rectangular sections 24 and 26 withthe rearward rectangular sections 26 being of greater length and widththan the forward rectangular section 24, but of equal height defining auniform cross sectional area of the base plate 20 that extends betweenan upper planar surface 28 and a lower planar surface 30.

Base plate 20 further comprises a forward or anterior end 32 and arearward or posterior end 34. A first or front longitudinal side 36 ofthe base 20 extends between the anterior and posterior ends 32 and 34with a step 38 at the transition edge between the rearward and forwardrectangular sections 24 and 26. Similarly, a second or rear longitudinalside 40 extends between the anterior and posterior ends 32 and 34 with astep 42 at the transition edge between the two rectangular sections 24,26.

Shuttle Assembly

Referring to FIGS. 4 and 5, shuttle assembly 44 comprises a linear guiderail 46 having a predetermined length attached on the upper planarsurface 28 of the base plate 20 along the central longitudinal axis 22thereof utilizing bolts 48 passing through guide rail holes 50 andthreading into guide rail base holes 52.

Additionally, the shuttle assembly 44 comprises a pair of shuttlebearing guides 54 and 56 that are slideably mounted on linear guide rail46 along its predetermined length.

The shuttle assembly 44 further comprises a shuttle 60 slideably mountedon linear guide rail 46 along its predetermined length via shuttlebearing guides 54, 56. Specifically, the shuttle 60 comprises twolongitudinally spaced apart pairs of four holes 62 disposed through anupper surface 64 of the shuttle at a fore and aft location thereof. Inturn, two pair of four bolts 66 respectively pass through the two pairof four holes 62 and thread into complementary spaced threaded bores 68disposed through the upper surface of each shuttle bearing guide 54, 56thereby slideably mounting the shuttle and any mounted labware onto thelinear guide rail 46 so that the shuttle is reciprocally movable alongthe predetermined length of the linear guide rail 46. Shuttle 60comprises a set of fore and aft locating apertures 61 (FIGS. 4) and 63(FIG. 5) for receipt of complementarily spaced labware locating pins.

Furthermore, the shuttle assembly 44 comprises motor 70 mounted on baseplate 20 proximate a posterior longitudinal corner of base plate 20 viaa generally inverted L-shaped bracket 72 having a horizontal landingattaching to motor 70 via motor bolts 74 and to the base plate 20 viabolts 76 threading into bores 78 of base plate 20 such that the motor isvertically spaced from the base plate 20 for defining a pulley space.Two pulleys 80 and 82, over which a timing belt 84 runs, are arrangedlongitudinally spaced apart by a predetermined distance and such thatthe timing belt 84 runs parallel with and between the linear guide rail46 and the rear longitudinal side 40 of the base plate 20. In oneembodiment, the length or span of the timing belt 84 along the baseplate 20 is greater than the length of the linear guide rail 46. Pulley80 is the driving pulley and is fitted within the pulley space under theL-shaped bracket 72 and is operatively coupled to the drive shaft of thebracket supported motor 70. The driven pulley 82 is rotateably supportedby a shaft 85 and a disk-shaped member 86 which is fitted into a pulleyattachment hole 88 disposed in base plate 20. The pair of pulleys 80,82, and timing belt 84 combine to function as drive linkage translatingrotary motion of the shaft of the motor 70 into linear motion of theshuttle 60 as further detailed below.

Moreover, and referring to FIGS. 5 and 6, the timing belt 84 isinterposed between a bent bracket 90 and a pair of fixing blocks 92, 94(FIG. 6). The bent bracket 90 is attached to the upper planar surface 64of the shuttle 60 via bolts 96. Thus, when the timing belt 84 runs overthe driving and driven pulleys 80, 82 the rotation of the motor 70 istranslated into linear motion of the shuttle 60 along the linear guiderail 46 in a direction away or toward a home position.

Referring to FIGS. 4 and 6, the shuttle assembly 44 further comprisesthe sensor target, trip, or flag member 98 attached to the rearlongitudinal side of the shuttle 60 via bolts 100.

Additionally, the shuttle assembly 44 comprises the two alignedlongitudinally spaced sensors 102 and 104 that are of an interrupt stylethat detect the presence of the flag member 98 passing adjacent ortherethrough. The two aligned longitudinally spaced sensors 102 and 104are secured to the base plate 20 via bolts 106 and 108 respectively.

Sensor 102 indicates when the shuttle 60 is in the predefined homeposition (a gripper and pipetter/probe head assembly accessible home)juxtaposed vertically above the forward rectangular section 24 of thebase plate 20. Similarly, sensor 104 indicates when the shuttle 60 is inthe predefined fully longitudinally extended position juxtaposedvertically above the rearward rectangular sections 26 of the base plate20. The triggering or detection signals are transmitted to thecontroller 400 and computer 520 for use in control of the rectilinearmovement of shuttle 60. In one embodiment, these are utilized withconventional internal motor encoding in locating shuttle 60 horizontallyalong linear guide rail 46.

Elevated Manifold Assembly

Referring back to FIG. 1, and as noted above, apparatus 10 furthercomprises an elevated manifold assembly 110 comprised of a manifoldframework assembly 112 supporting a manifold plate assembly 160 in asubstantially horizontal plane parallel to and vertically above theupper planar surface 28 of the base plate 20 at a predetermineddistance.

Manifold Framework Assembly

Now referring to FIGS. 1 and 4, manifold framework assembly 112comprises an inverted, generally U-shaped vertical support plate 114vertically upwardly extending from the upper planar surface 28 of thebase plate 20. In one embodiment, the U-shaped vertical support plate114 is disposed at an anterior latitudinal edge of the secondrectangular section 28 of base plate 20 immediately adjacent the firstrectangular section 24 in a plane substantially perpendicular to thelongitudinal axis 22 of the base plate 20. Bolts 116 extend through thelower planar surface 28 of the base plate 20 and threadedly couple withthreaded blind bores disposed through horizontal planar ends 118, 120 ofU-shaped vertical support plate 114 for fixedly attaching the supportplate 114 to base plate 20.

Vertical support plate 114 has a substantially uniform U-shapedcross-sectional area and comprises a transverse member 122 having outerends transitioning into a pair of generally parallel vertical main framemembers 124, 126 terminating into the horizontal planar ends 118, 120.

The vertical support plate 114 further comprises a substantially planarvertical anterior or exterior surface 128 and a substantially planarvertical posterior or interior surface 130 (FIG. 9) spaced from theanterior surface 128. As illustrated in FIG. 4, the vertical supportplate 114 comprises an outer periphery defined by a horizontallydisposed upper exterior surface of the transverse member 122 andgenerally parallel vertical exterior side surfaces of respective mainframe members 124, 126.

Additionally, the vertical support plate 114 comprises a generallyU-shaped inner peripheral surface 136 defining a U-shaped opening 138.The U-shaped inner periphery or surface 136 comprises a horizontallydisposed upper interior surface having opposing ends that arcuatelytransition downwardly into generally parallel vertical interior sidesurfaces of respective main frame members 124, 126 wherein the interiorside surfaces transition into respective recessed surfaces 140, 142defining interiorly notched lower ends of respective main frame members124, 126.

Referring to FIGS. 4 and 5, the U-shaped opening 138 is centrallydisposed through the vertical support plate 114 such that the centralvertical axis of both are coincident and defined by a central verticalaxis 144 of the vertical support plate 114. The central vertical axis144 of the vertical support plate 114 is normal to and coplanar with thecentral longitudinal axis 22 of the base plate 20 and the linear guiderail 46 that is disposed along central longitudinal axis 22. Verticalmain frame members 124, 126 are equally latitudinally spaced from thecentral vertical axis 144 of the vertical support plate 114 for allowingthrough passage of the shuttle 60 with or without supported lab ware toshuttle between the first predefined home position (the gripper andpipetter/probe head assembly accessible home) juxtaposed verticallyabove the forward rectangular section 24 of the base plate 20 and thesecond predefined fully longitudinally extended position juxtaposedvertically above the rearward rectangular sections 26 of the base plate20.

Additionally, vertical manifold framework assembly 112 comprises twovertical support rods 146 and 148 longitudinally disposed apredetermined distance posterior to and in respective parallel relationwith the vertical main frame members 124, 126 of the vertical supportplate 114. Rods 146 and 148 are attached to the base plate and manifoldplate assembly with bolts 150. Spacers 147, 149 circumscribe respectiverods 146,148 adjacent the upper surface 28 of base plate 20.

Furthermore, vertical manifold framework assembly 112 comprises alongitudinally rearward or back central vertical support plate 152. Backcentral vertical support plate 152 has a substantially rectangular shapewith a substantially uniform cross section with the exception of ananterior recessed portion 154. In one embodiment, recessed portion 154provides extra clearance for the shuttle 60 with or without supportedlabware. The faces and edges of the support plate 152 are substantiallyplanar. The rearward central vertical support plate 152 verticallyupwardly extends from the base plate 20 in a plane substantiallyperpendicular to the base plate 20. Bolts 156 extend through the lowerplanar surface 28 of the base plate 20 and threadedly couple withthreaded blind bores disposed through horizontally inferior planar endof back central vertical support plate 152 for fixedly attaching theplate 152 to base plate 20.

Referring to FIG. 5, the back central vertical support plate 152comprises a central vertical axis 158 that is normal to and coplanarwith the central longitudinal axis 22 of the base plate 20 and thelinear guide rail 46 that is disposed along central longitudinal axis22. Accordingly, vertical axis 144 and vertical axis 156 arelongitudinally aligned and spaced by a predefined longitudinal distance.

Manifold plate assembly

Referring to FIGS. 1 and 7, and as noted above, the elevated manifoldassembly 110 comprises the manifold plate assembly 160 disposed in asubstantially horizontal plane parallel to and vertically above theupper planar surface 28 of the base plate 20 at a predetermineddistance.

As illustrated in the embodiment of FIG. 7, the manifold plate assembly160 comprises a top plate 162 conventionally coupled to a manifold 164via a manifold top plate gasket 166 sandwiched between the top plate 162and manifold 164. The manifold plate assembly 160 further comprises aninferiorly disposed plate gasket 168 attached to an inferior or bottomsurface of the manifold 164.

As illustrated, a multiplicity of bolts 169 are utilized to attach themanifold to the superior horizontal planar surface of the verticalsupport plate 114 and the back central vertical support plate 152 and tofurther attach to rods 146 and 148. Additionally, a plurality of bolts169 are utilized to attach manifold 164 to top plate 162 with themanifold top plate gasket 166 interposed therebetween and with themanifold 164 carrying the inferiorly disposed plate gasket 168.

The manifold controlled pressure source assembly includes a pressureline 552 (FIG. 3) operatively coupling to the manifold in a conventionalmanner via elbow fitting 554 (FIG. 14) disposed through top plate 162 ofthe manifold plate assembly 160.

PCB Housing and Forward End Cap

Positive pressure SPE apparatus 10 further comprises a PCB housing 170comprising the posterior latitudinal plate 172 vertically extending fromand attached to a reward lateral upper planar edge of base plate 20 viabolts 174 and a horizontal plate 176 attached to the latitudinal plate172 via bolts 178. The housing 170 further comprises a pair oflatitudinally spaced apart and longitudinally offset rods 180, 182 thatare attached to base plate 20 via bots 184 (FIG. 4) and to horizontalplate 176 via bolts 186.

Positive pressure SPE apparatus 10 further comprises end cap 188vertically extending from and attached to a forward lateral upper planaredge of base plate 20 via bolts 190.

Waste Tray Assembly

Referring to FIGS. 7, 9, and 10, the waste tray assembly 560 comprises awaste tray 580 located on shuttle 60 via locating pins in the waste traymating with locating apertures in the shuttle 60. The waste tray 580having an interior floor with a posteriorly downwardly tapering portionleading to a waste try outlet 581 extending through the posterior wallof waste tray 580 and operatively coupling with elbow fitting 582. Inturn, elbow fitting 582 is operatively coupled to one end of a flexibleline 584 as illustrated in FIG. 10.

The flexible line 584 moves with the waste tray 580 and line 584 has anopposing end in open fluid coupling communication with the waste line562 of the waste assembly 560 (FIG. 3).

Additionally, waste tray 580 comprises two pair of side ears 585 withpairs disposed on opposing longitudinal sides of the waste tray withlocator receiving apertures 586 disposed in the rear longitudinal pairof side ears 585 which are captured by the lower tiered lift device 230and in particular by one or more mating pins 231 disposed on an interiorledge support member 236 being received within an underside apertures586 disposed in the rear longitudinal pair of side ears 585 ascontrollably aligned by the shuttle 60.

Filter and Collection Plates

Additionally, and referring to FIG. 7 through 10, a filter plate fittingring 588 surmounts and circumscribes waste tray 580 and is provided withan overhang 589 on each side which is captured by the upper tiered liftdevice 280 and in particular by one or more mating pins 281 disposed onan interior ledge “U” shaped member 318 being received within anunderside aperture of the overhang 589 as controllably aligned when theshuttle 60 is positioning, for example, a filter plate 590 (FIG. 15) tothe upper lift device 280.

Furthermore, collection plate 600 is configured to surmount the wastetray 580 and be lifted therewith by the lower lift device 230 presentingit, for example, to the filter plate 590 with a controllable height Hbetween collection plate 600 and the filter plate 590 as is illustratedin FIG. 28.

Tiered Elevator Lift Assembly

Referring to FIG. 1, and as noted above, the positive pressure solidphase extraction (SPE) apparatus 10 further comprises the tieredelevator lift assembly 192. Tiered elevator lift assembly 192 comprisesthe upper lift device 280, the lower lift device 230, and vertical guiderail assembly comprising three triangularly disposed vertical trackways196, 198, and 200 (FIGS. 4 and 9).

Vertical Guide Rail Assembly

Referring to FIGS. 4 and 5, the vertical guide rail assembly comprisesthree triangularly disposed vertical trackways 196, 198, and 200 eachhaving a predetermined length.

Parallel spaced apart vertical trackways 196, 198 are respectivelydisposed on the posterior or interior surfaces of vertical main framemembers 124, 126 in a plane parallel to vertical axis 144 of verticalsupport plate 114 and perpendicular to central longitudinal axis 22 ofthe base plate 20. Each of the vertical trackways 196, 198 are at anequal latitudinal distance from the central vertical axis 144 and thecentral longitudinal axis 22 of the base plate 20 and the linear guiderail 46 disposed thereon. Bolts 199 attach the parallel spaced apartvertical trackways 196, 198 to respective posterior surfaces of verticalmain frame members 124, 126 of vertical support plate 114 as bestillustrated in FIG. 9.

Trackway 200 is disposed on the posterior or interior surface of backcentral vertical support plate 152 such that the vertical central axisof the trackway 200 is coincident with the central vertical axis 158 ofthe back central vertical support plate 152. Accordingly, the verticalcentral axis of the trackway 200 (axis 158) is substantially normal toand coplanar with the central longitudinal axis 22 of the base plate 20and the linear guide rail 46 that is disposed along central longitudinalaxis 22. Additionally, the vertical axis of the three triangularlydisposed vertical trackways 196, 198, and 200 are substantially parallelwith one another and are spaced apart by a predefined distance.

The guide rail assembly further comprises a pair of bearing guidesslideably mounted on each of the vertical trackways 196, 198, and 200 ina vertically tiered fashion. Specifically, a first lower bearing guide202 and a first upper bearing guide 204 are slideably mounted ontrackway 196; a second lower bearing guide 206 and a second upperbearing guide 208 are slideably mounted on trackway 198; and a thirdlower bearing guide 210 (FIG. 6) and a third upper bearing guide 212(FIG. 10) are slideably mounted on trackway 200.

As will be further delineated below, the guide rail assembly furthercomprises six L-shaped lift coupling brackets 214, 216; 218, 220; 222,224 respectively attached to the six bearing guides 202, 204; 206, 208;and 210, 212 via bolts 226 (FIG. 6) for slideably coupling the lowerlift device 230 and the upper lift device 280 to vertical trackways 196,198, and 200 in a vertically tiered fashion.

Lower Lift Device

Referring to FIG. 5, and in one embodiment, the lower lift device 230comprises a substantially “U” shaped or forked lower lift member 232.Forked lower lift member 232 comprises laterally spaced longitudinalsupport members 234, 236 positioned to extend parallel andlongitudinally relative to the central axis 22 of the base plate 20 andopen towards the shuttle 60 so as to define an open receiving areabetween the longitudinal support members 234, 236 so dimensioned forunobstructed receipt of shuttle 60 with mounted labware thereon.

Members 234, 236 are respectively provided with clearance openings 238,240 for receipt of the rods 146, 148 therethrough. Members 234, 236 alsoemploy upper lift bump stops 242, 244.

Additionally, support members 234, 236 of the lower lift member 232respectively comprise recessed portions 246, 248 for allowing the upperlift device 280 and the lower lift device 230 to mate in a closeproximate vertically tiered juxtaposition as illustrated in FIG. 7. Inturn, recessed portions 246, 248 respectively comprise clearanceopenings 250, 252 for lead screws 306 and 316 to extend therethroughunhindered.

Furthermore, support members 234, 236 of the lower lift member 232respectively comprise terminating ends or guide pads 254, 256 thatcouple to the vertical guide rails 196 and 198. Specifically, guide pad254 sits on and is attached to the lower branch of inwardly turnedL-shaped lift coupling bracket 214 via a plurality of bolts 226 and, inturn, bracket 214 is bolted via bolts 226 to bearing guide 202 that isslideably coupled to vertical trackway 196 as illustrated in at leastFIGS. 5 and 6. Similarly, guide pad 256 sits on and is attached to thelower branch of inwardly turned L-shaped lift coupling bracket 218 via aplurality of bolts and, in turn, bracket 218 is bolted via bolts tobearing guide 206 that is slideably coupled to vertical trackway 198.Additionally, and as illustrated in FIG. 6, a U-shaped bracket 262 isbolted to the underside of the lower lift member 232 via bolts 264 andcomprises L-shaped lift coupling bracket 222 bolted to the bearing guide210 via a plurality of bolts 226 wherein the bearing guide 210 isslideably coupled to vertical trackway 200.

Accordingly, the vertical guide rail assembly provides a three pointslideable linkage to the lower elevator device 230.

Linear Actuator

Referring to FIG. 5, the lower lift device 230 further comprises alinear actuator 270 in the form of, but not limited to a stepper motorlinear actuator 270.

As illustrated in FIG. 6, the linear actuator 270 comprises a motorassembly 272 mounted to the lower lift member with bolts 274. Referringto FIGS. 1 and 5, the linear actuator 270 comprises a vertical threadedscrew 276 fixedly non-rotateably mounted in the top plate 162 of themanifold plate assembly 160 via axial translation preclusion nut 278.

In one embodiment, the motor assembly 272 comprises a reversible motoroperatively coupled to a nut that is routed vertically up and down onthe threaded screw 276 in response to reversible motor actuation by thecontroller 400 under orchestration by computer 520 wherein the motorassembly attached lower lift member 232 is vertically raised or loweredby controlled rotation of the motor for obtaining a predetermined orcontrollable height of the lower lift member 232 and labware mountedthereon. As noted above, the lower lift member 232 is further guided bybearing guide 210 slideably coupling the lower lift member 232 to guiderail 200.

Upper Lift Device

Referring now to FIGS. 8 through 10, and in one embodiment, the upperlift device 280 comprises a substantially “U” shaped or forked upperlift member 282, linear actuators 300, 310, a motor assembly 330, coggedpulley assembly comprising a first cogged pulley 342 (FIG. 8) and asecond cogged pulley 352 (FIG. 10), and belts 364, 366, and 368.

Forked Upper Lift Member

Forked upper lift member 282 comprises laterally spaced longitudinalsupport members 284, 286 positioned to extend parallel andlongitudinally relative to the central axis 22 of the base plate 20 andopen towards the shuttle 60 so as to define an open receiving areabetween the longitudinal support members 284, 286 so dimensioned forunobstructed receipt of shuttle 60 with mounted labware thereon.

Members 284, 286 are respectively provided with clearance openings forreceipt of rods 146, 148 and vertical threaded screw 276 therethrough.

Additionally, support members 284, 286 of the upper lift member 282respectively comprise terminating ends or guide pads 288, 290 thatcouple to the vertical guide rails 196, 198. Specifically, guide pad 288sits on and is attached to the lower branch of inwardly turned L-shapedlift coupling bracket 216 via a plurality of bolts 228 and, in turn,bracket 216 is bolted via bolts 228 to bearing guide 204 that isslideably coupled to vertical trackway 196. Similarly, guide pad 290sits on and is attached to the lower branch of inwardly turned L-shapedlift coupling bracket 220 via a plurality of bolts 228 and, in turn,bracket 220 is bolted via bolts 228 to bearing guide 208 that isslideably coupled to vertical trackway 198.

Additionally, and as illustrated in FIG. 10, a U-shaped bracket 292 isbolted to the top side of the upper lift member 282 via bolts 294 andcomprises L-shaped lift coupling bracket 224 bolted to the bearing guide212 via a plurality of bolts 226 wherein the bearing guide 212 isslideably coupled to vertical trackway 200. Accordingly, the verticalguide rail assembly provides a three point slideable linkage to theupper elevator device 280.

Linear Actuators

Still referring to FIGS. 8 through 10, the upper lift device 280 furthercomprises a pair of parallel latitudinally spaced apart verticallyextending stepper motor linear actuators 300, 310 (FIG. 9) that areequidistance from central longitudinal axis 22.

Front Actuator

In one embodiment, linear actuator 300 is in the form of a lead nutlinear actuator that comprises a lead nut drive pulley assembly 302surmounting an access aperture 320 in support member 284 of the forkedupper lift member 282 that is coaxial with the clearance hole 250 (FIG.5) in support member 234 of forked lower lift member 232.

Additionally, the linear actuator 300 comprises a lead nut drive pulleyinterface assembly 304 that passes through aperture 322 in a “U” shapedlead nut bearing support 308 for providing an interfacing coupling withlead nut drive pulley interface assembly 302 that captures supportmember 284. The lead nut bearing support 308 attaches to the undersideof support member 284 and is allowed to mate in a close proximatevertically tiered juxtaposition with support member 234 of the lowerlift member 232.

As illustrated, the lead screw 306 operatively passes through both thelead nut drive pulley assembly 302 and the interface assembly 304. Atone end, the lead screw 306 is attached to base plate 20 and at theopposing end to top plate 162 via respective axial translationpreclusion nuts 278 (FIG. 7).

Rear Actuator

In one embodiment, linear actuator 310 is in the form of a lead nutlinear actuator that comprises a lead nut drive pulley assembly 312surmounting an access aperture 322 in support member 286 of the forkedupper lift member 282 that is coaxial with the clearance hole 252 (FIG.5) in support member 236 of forked lower lift member 232.

Additionally, the linear actuator 310 comprises a lead nut drive pulleyinterface assembly 314 that passes through aperture 324 in a “U” shapedlead nut bearing support 318 for providing an interfacing coupling withlead nut drive pulley interface assembly 312 that captures supportmember 286. The lead nut bearing support 318 attaches to the undersideof support member 286 and is allowed to mate in a close proximatevertically tiered juxtaposition with support member 236 of the lowerlift member 232.

As illustrated, the lead screw 316 operatively passes through both thelead nut drive pulley assembly 312 and the interface assembly 314. Oneend of lead screw 316 is attached to base plate 20 and the opposing endto top plate 162 via respective axial translation preclusion nuts 278.

Motor Assembly

Referring now to FIGS. 8 and 9, and in one embodiment, the upper liftdevice 280 further comprises motor assembly 330. Motor assembly 330comprises reversibly excitable motor 332 mounted proximate a posteriorcorner of forked upper lift member 282 via a generally “U” shaped motorbracket 334. The generally “U” shaped motor bracket 334 is turnedsideways for providing a horizontal landing attaching to motor 332 viamotor bolts 336 and a spaced landing attaching to the upper surface ofthe upper lift device 280 via bolts 338 such that the space between thelandings or horizontally extending sides of bracket 334 define a coggedpulley space for receiving a cogged pulley assembly 342 that isoperatively coupled to reversibly excitable motor 332 as detailed below.

Cogged Pulley Assembly

Now referring to FIGS. 8 through 10, and as noted above, an embodimentof the upper lift device 280 further comprises a first cogged pulley 342assembly (FIG. 8) and a second cogged pulley assembly 352 (FIG. 10).

First cogged pulley assembly 342 is received within the cogged pulleyspace defined by horizontally extending sides of bracket 334 and isoperatively coupled to motor 332 for rotation thereby. First coggedpulley assembly 342 comprises a first horizontally disposed lower coggedpulley 344 and a first horizontally disposed upper cogged pulley 346.

Second cogged pulley assembly 352 comprises a second horizontallydisposed lower cogged pulley 354 and a second horizontally disposedupper cogged pulley 356 vertically pinned for rotation in a sidewaysdisposed “U” shaped bracket 358. Utilizing bolts 360, bracket 358 isattached to the upper surface of the forked upper lift member 282 at aposterior corner that latitudinally opposes the first cogged pulley 342for latitudinally aligning the second cogged pulley assembly 352 withthe first cogged pulley assembly 342 at a complemental height.

Belts

A first cogged belt 364 is latitudinally passed around the upper coggedpulley 346 of the first cogged pulley assembly 342 and the upper coggedpulley 356 of the second cogged pulley assembly 352.

In turn, a second cogged belt 366 is longitudinally passed around thelower cogged pulley 344 of the first cogged pulley assembly 342 andaround a first cogged lead nut drive pulley 301 of the lead nut drivepulley assembly 302.

Likewise, a third cogged belt 368 is longitudinally passed around thelower cogged pulley 354 of the second cogged pulley assembly 352 andaround a second cogged lead nut drive pulley 311 of the lead nut drivepulley assembly 312.

The respective upper and lower cogged pulleys are rotateably fixedtogether such that the motor drives the upper and lower cogged pulley346, 344 in unison and such that the upper and lower cogged pulleys 356,354 are also driven in unison.

Accordingly, directional rotational actuation of the single motor 332results in the simultaneous liner actuation of linear actuators 300, 310for raising and lowering the forked upper lift member 282 with the motor332 onboard thereof

Specifically, when motor 332 is actuated, the lower cogged pulley 344and the upper cogged pulley 346 are driven thereby translating motion tothe cogged belt 366 for driving the first cogged lead nut drive pulley301 while simultaneously driving the second cogged lead nut drive pulley311 with the cogged belt 368 receiving motion from the second lowercogged pulley 354 which, in turn, receives motion from the second uppercogged pulley 356 receiving motion by cogged belt 364 being driven bythe first upper cogged pulley 346 for vertically raising and loweringthe forked upper lift member 282 with the motor 332 onboard bytransforming the rotation of the motor to the liner actuation of linearactuators 300, 310 wherein the forked upper lift member 282 is raisedand lowered in a substantially horizontal plane substantially parallelwith base plate 20 and top plate 160.

In one embodiment, and as illustrated in FIG. 11, apparatus 10 furthercomprises a pair of forward longitudinal side protective plates 370, 372and a pair of rearward longitudinal side protective plates 374, 376.

Use and Operation

The use and operation of apparatus 10 will be further delineated by anexample, but it is to be understood that multiple positive pressure SPEprocesses are completed along with multiple plate management scenariosbeing solved and provided by the two tier plate mounting scheme of theshuttle 60.

Accordingly, reference is made to FIG. 12 for outlining this positivepressure SPE process example with FIG. 13 providing further detailsthereof which are diagrammatically illustrated in FIGS. 14 through 30described below.

At the outset, FIG. 14 illustrates the automated positive pressure SPEapparatus 10 in an initialized state with the lower and upper lifts 230,280 in a lower initial loading position and the shuttle assembly 44 inthe home position surmounted by a waste tray 580 which is, in turn,surmounted by filter plate fitting ring 588 having overhang 589.

FIG. 15 illustrates the automated positive pressure SPE apparatus 10receiving labware in the form of a filter plate 590 from the engagingfingers or gripper 452 of the automated pipetting workstation 420wherein the filter plate 590 is tiered above and mates with, via thefilter plate fitting ring 588, the waste tray 580 that is mounted on theshuttle 60 of the shuttle assembly 44 located at the accessible positionof the gripper and pipetter or probe head assembly of the automatedpipetting workstation 420 for locating the filter plate and performing aconditioning step comprising dispensing a conditioning agent into thefilter plate 590 at the accessible position while capturing all fluidswhich are pushed through the filter plate 590 in the conditioning step.

FIG. 16 illustrates the automated positive pressure SPE apparatus 10with the shuttle assembly 44 transported within the elevated manifoldassembly 110 and the filter plate 590 positioned via sensors describedabove over locating pins of the upper elevator device 280 to ensurepositional accuracy while the filter plate 590 is being lifted up toengage the manifold 164 while simultaneously presenting the waste trayover locating pins of the lower elevator device 230 to ensure positionalaccuracy while the waste tray 580 is being lifted up to engage under thefilter plate 590 engaged under the manifold plate 164.

FIG. 17 illustrates the automated positive pressure SPE apparatus 10presenting the filter plate 590 to the manifold plate 164 with the upperelevator 280 and positioning the waste tray 580 with the lower elevatordevice 230 during the conditioning phase. In one embodiment, theshuttle, with the waste tray 580, remains in the elevator frameworkwhile the filter plate 590 is being lifted. Once the filter plate 590has been positioned against the manifold plate 164 the waste tray 580 isthen brought up beneath the filter plate 590 via the lower lift device230. Positive pressure is then applied to the manifold 164 which in turnpushes the conditioning fluid out of the filter plate 590 into the wastetray 580. The waste fluid is then siphoned out of the apparatus 10.

FIG. 18 illustrates the automated positive pressure SPE apparatus 10with the filter plate 590 repositioned back to the automated pipettingworkstation accessible position and the elevator assemblies 230, 280down with the condition process completed to allow the pipetter todispense the sample to be separated into the filter plate 590.

FIG. 19 illustrates the automated positive pressure SPE apparatus 10with the shuttle assembly 44 transported back within the elevatedmanifold assembly 110 and the filter plate 590 positioned via sensorsover locating pins of the upper elevator device 280 to ensure positionalaccuracy while the filter plate 590 is being lifted up to engage themanifold 164 while simultaneously presenting the waste tray 580 overlocating pins of the lower elevator device 230 to ensure positionalaccuracy while the waste tray 580 is being lifted up to engage under thefilter plate 590 engaged under the manifold plate 164.

FIG. 20 illustrates the automated positive pressure SPE apparatus 10presenting the filter plate 590 with the sample therein to the manifold164 with the upper elevator device 280 and positioning the waste trough580 with the lower elevator device 230 during the sample addition phase.In one embodiment, the shuttle assembly 44, with the waste tray 580,remains in the elevator framework 110 while the filter plate 580 withthe sample therein is being lifted. Once the filter plate 580 has beenpositioned against the manifold plate 164 the waste tray 580 is thenbrought up beneath the filter plate 590 via the lower elevator device230. Positive pressure is then applied to the manifold 164 and the wastefluid is then siphoned out of the apparatus 10.

FIG. 21 illustrates the automated positive pressure SPE apparatus 10with the filter plate 590 repositioned back to the automated pipettingworkstation accessible position and the elevator assemblies 230, 280down to allow the pipetter to dispense a washing agent into the filterplate 590.

FIG. 22 illustrates the automated positive pressure SPE apparatus 10with the shuttle transported back within the elevated manifold assembly110 and the filter plate 590 with the washing agent positioned viasensors over locating pins of the upper elevator assembly 280 to ensurepositional accuracy while the filter plate 590 is being lifted up toengage the manifold plate 164 while simultaneously presenting the wastetray 580 over locating pins of the lower elevator device 230 to ensurepositional accuracy while the waste tray 580 is being lifted up toengage under the filter plate 590 engaged under the manifold plate 164.

FIG. 23 illustrates the automated positive pressure SPE apparatus 10presenting the filter plate 590 with the washing agent therein to themanifold 164 with the upper elevator device 280 and positioning thewaste tray 580 with the lower elevator device 230 during the washingphase. In one embodiment, the shuttle assembly 44, with the waste tray580, remains in the elevator framework 110 while the filter plate 590with the washing agent therein is lifted. Once the filter plate 590 ispositioned against the manifold plate 164 the waste tray 580 is thenbrought up beneath the filter plate 590 via the lower lift device 230.Positive pressure is then applied to the manifold and the waste fluid isthen siphoned out of the apparatus 10.

FIG. 24 illustrates the automated positive pressure SPE apparatus 10with the lower elevator device 230 at the home position, the shuttleassembly with the waste tray 580 repositioned back to the automatedpipetting workstation accessible position or the shuttle home to allowthe pipetter to place the collection plate 600 on the shuttle while theupper elevator device 280 maintains the vertical abutment of the filterplate 590, with the remaining sample therein, below the manifold plate164.

FIG. 25 illustrates the automated positive pressure SPE apparatus 10with the collection plate 600 transported within the elevated manifoldassembly 110 and positioned via sensors over locating pins of the lowerelevator device 230 to ensure positional accuracy while the collectionplate 600 is being lifted up to engage under the filter plate 590engaged under the manifold plate 164 to allow the upper elevator device280 to lower the filter plate onto the collection plate 600.

FIG. 26 illustrates the automated positive pressure SPE apparatus 10with the elevator assemblies 230, 280 in relatively down positions withthe shuttle assembly 44 transported back to the automated pipettingworkstation accessible position with both the collection plate 600 andfilter plate 590 thereon to allow the pipetter to dispense an elutionagent to the filter plate 590.

FIG. 27 illustrates the automated positive pressure SPE apparatus 10with the shuttle assembly 44 and both the collection plate 600 andfilter plate 590 comprising elution agent disposed thereon transportedwithin the elevated manifold assembly 110 with the filter plate 590comprising elution agent positioned via sensors over locating pins ofthe upper elevator device 280 to ensure positional accuracy while thefilter plate 590 is being lifted up to engage the manifold plate 164while simultaneously presenting the collection plate 600 over locatingpins of the lower elevator assembly to ensure positional accuracy whilethe collection plate 600 is being lifted up to engage the nozzles on thefilter plate which, in turn, is engaged under the manifold plate 164.

FIG. 28 illustrates the automated positive pressure SPE apparatus 10with the filter plate 590 with the elution agent therein engaged withthe manifold 164 by the upper elevator device 280 and further shown withthe collection plate 600 engaged with the filter plate 590 wherein thenozzles of the filter plate aligned with wells of the collection plateto preclude cross-contamination.

FIG. 29 illustrates the automated positive pressure SPE apparatus 10with the collection plate 600 shuttled back to the automated pipettingworkstation accessible position to allow the pipetter to remove thecollection plate 600 from the shuttle assembly 44.

FIG. 30 illustrates the automated positive pressure solid phaseextraction apparatus 10 presenting the filter plate 590 back to theautomated pipetting workstation accessible position to allow thepipetter to remove the filter plate 590 from the shuttle assembly 44.

Accordingly, and in one aspect, the upper and lower lift members and theshuttle are individually controlled for vertically shuttling labwareinto the tiered elevator lift assembly and respectively handing it offto the upper and lower lifts tiered lift devices of the tiered elevatorlift assembly for lifting one labware piece or two tiered labware piecesup to the manifold plate for processing while simultaneously displacingthe shuttle back to the gripper and pipetter/probe head assemblyaccessible home position in accordance with the steps of the currentuser defined or predefined SPE process.

Examples of the automated pipetting workstations including software arepresently manufactured and sold by the assignee of the present patentapplication, Hamilton Company, 4970 Energy Way, Reno, Nev. 89502, UnitedStates Of America.

FIG. 31 is a perspective view illustrating a plurality of the automatedpositive pressure SPE apparatuses 10 disposed on a rear lateral deckportion of another embodiment of an automated pipetting workstation 1010only framework of which is illustrated for clarity of illustration ofeach SPE apparatus 10 disposed on the deck.

Evaporator

Referring to FIG. 32, and in another aspect, an embodiment of theinvention provides an automated positive pressure SPE apparatus 10further comprising a heater control unit 700 for adding heat to thesystem air for serving as an evaporator for downstream SPE processes.

Referring to FIG. 33, a general flow diagram of an embodiment of anautomated positive pressure SPE process is illustrated furthercomprising an evaporation process that is detailed in FIG. 34 anddiagrammatically illustrated in FIGS. 35 through 42.

As described above, software controls the automated pipettingworkstation 420 and positive pressure solid phase extraction apparatus10.

Referring to FIGS. 34 and 35, and at the outset of the evaporationprocess, the automated pipetting workstation 420 is software controlledto place an evaporator adapter 710 onto the shuttle 60 of the positivepressure solid phase extraction apparatus 10 thereby receiving byapparatus 10 the evaporator adapter 710 from the automated pipettingworkstation 420 as illustrated in FIG. 35.

Next, apparatus 10 then moves the evaporator adapter 710 to the manifold164 via software control for presenting the evaporator adapter 710 tothe manifold 164 with the upper elevator 280 as illustrated in FIG. 36.

Apparatus 10 then moves the shuttle 60 to the automated pipettingworkstation accessible position via software control for presenting theshuttle 60 back to the pipetting accessible position to allow thepipetter to place a collection plate 810 on the shuttle 60 asillustrated in FIG. 37.

As illustrated in FIGS. 38 and 39, and under software control, thecollection plate 810 is then moved by the apparatus 10 for presentingthe shuttle 60 with the collection plate 810 back to the lower elevator230 which is then software controlled to lift the collection plate 810to engage the needles of the evaporator adapter 710 just above theliquid height in the collection plate 810. Then, user specified heatedair is applied to the liquid surface for a use specified time period toevaporate the liquid and leaving behind the solute.

Referring to FIG. 40, the evaporated vapors are directed through aplenum 820 to a duct 822 which is connected to the user's ventilationsystem. During the evaporation process, the lower tiered lift device 230moves to keep the liquid being evaporated in close proximity to theevaporator adapter 710 to maximize efficiency of the evaporationprocess.

As illustrated in FIG. 41, apparatus 10 then moves the shuttle 60 withthe collection plate 810 back to the pipette accessible position viasoftware control for presenting the collection plate 810 back to theautomated pipetting workstation accessible position for removal of thecollection plate 810 from the shuttle 60 by the automated pipettingworkstation 420 via software control.

As illustrated in FIG. 42, apparatus 10 then collects the evaporatoradapter 710 and moves the shuttle 60 with the evaporator adapter 710back to the pipette accessible position via software control forpresenting the evaporator adapter 710 back to the automated pipettingworkstation accessible position for removal by the automated pipettingworkstation 420 via software control.

Accordingly, the above delineated evaporation process comprises placingan evaporator adapter 710 onto the shuttle assembly 60 which presentsthe adapter 710 to the upper tiered lift device 280. The upper tieredlift device 280 presents the evaporator adapter 710 to the manifoldplate 164 through which the apparatus controls both the flow viamanifold pressure source assembly 550 and heat added via the heatercontrol unit 700 to the system air.

Subsequently, this air flows through the evaporator adapter 710 intolabware 810 which is presented to the adapter 710 by the lower tieredlift device 230. The labware 810 is presented in close proximity to theevaporator adapter 710 such that the controlled heated air is directedonto the liquid surface to be evaporated without the adapter 710 beingin direct contact with the liquid being evaporated. The evaporatedvapors are directed through the plenum 820 to the duct 822 which isconnected to the user's ventilation system.

During the evaporation process, the lower tiered lift device 230 movesto keep the liquid being evaporated in close proximity to the evaporatoradapter 710 to maximize efficiency of the evaporation process.

Process Security System 900

Referring to FIG. 43, and in another aspect, an embodiment of theautomated positive pressure SPE apparatus 10 further comprises a processsecurity system 900 for providing process security by use of a pressuresensor system 910 and a temperature sensor system 920 respectivelycomprising pressure sensors 912 and temperature sensors 922 that monitorthe pressure and temperature change over time for an array of wells, forexample up to 96 wells, during the SPE process.

The use of the pressure sensors 912 provides process security for eachwell of the labware by collecting pressure data which the processsecurity system 900 utilizes to construct a curve 914 of the processutilizing computer/controller 520 delineated in detail above. This curveis then compared by the process security system 900 viacomputer/controller 520 to a previously stored standard acceptable curve916 with tolerance boundaries defined from which a pass/error decisionis made by the process security system 900 regarding the completenessand timeliness of the process being measured.

Typically, one or more standard acceptable curves 916 are stored innon-transitory computer-readable medium 530. The Errors are presented tothe user and recorded permanently in a log file with time and date fortraceability. The log file can also be stored in non-transitorycomputer-readable medium 530.

The temperature sensors 922 provide additional process security inapplications that are sensitive to temperature variances by recordingthe temperature 924 of each well in the labware at various times duringthe process and having, for example, one or more bench mark temperatures926 to which the recorded temperatures 924 are compared to for makingdecision. The one or more bench mark temperatures 926 and recordedtemperatures 924 can be stored in non-transitory computer-readablemedium 530.

Temperature values are also recorded permanently in a log file with dateand time for traceability and future use. The log file can also bestored in non-transitory computer-readable medium 530. Errors arepresented to the user and recorded permanently in the log file with timeand date for traceability.

Tip Dryer

In another aspect, an embodiment of the invention provides an automatedpositive pressure SPE apparatus 10 that serves as a tip dryer by meansof presenting a rack of tips to the upper tiered lift device 280 by theshuttle assembly 60. The upper tiered lift device 280 presents the rackof tips to the manifold plate through which the apparatus controls theflow of controlled heated air provided by heater control unit 700.Subsequently, this air flows through the individual tips and any liquidis captured by the shuttle assembly 60 and directed to a liquid wastecontainer 564 (FIG. 32).

Cap Mat Sealing

In another aspect, an embodiment of the invention provides an automatedpositive pressure SPE apparatus 10 that serves as a cap mat sealingdevice. First, labware is place on the shuttle assembly 60. Then a capmat is placed onto the top of the labware. The shuttle assembly 60presents the stack to the upper tiered lift device. The upper tieredlift device presents the stack to the manifold plate and applies forceas if attempting to seal the labware against the manifold plate 164 inthe SPE process. This will seat the cap mat into the labware. Airpressure can be additionally applied to further seat the cap mat intothe labware to create the necessary seal.

Lowering Profile Outboard Motor Positioning Assembly

Referring to FIGS. 44 through 46, and in another aspect, an embodimentof the automated positive pressure SPE apparatus 10 further comprisesdisposing motor 332 outboard of the upper elevator lift 280 for loweringthe height or profile of the apparatus 10.

In essence, the motor 332 and the supporting “U” shaped motor bracket334 are moved off the upper elevator lift device 280 and posteriorlydisposed from the posterior corner that latitudinally opposes the secondcogged pulley assembly 352. The motor 332 is operatively coupled to theinferiorly disposed cogged pulley 346 at its outboard location.

In turn, a ball spline assembly 380 is provided having an inferiorlydisposed pulley drive 382 coupled to a cogged pulley 345 operativelycoupled to the cogged pulley 346 driven by reversibly excitable motor332 via a belt 384.

The ball spline assembly 380 passes through the lower tiered lift devicevia aperture 390 and the upper tiered lift device via aperture 392.

Disposed above the upper tiered lift device is a bushing jacket spline394 taking the place of assembly 342 at a complemental height with thebelts 364, 366 operatively coupled thereto for rotation therewith whenbelt 384 is driven by motor 332 and wherein the rotation of belt 364engenders the rotation of belt 368 via the second cogged pulley assembly352 as detailed above.

The above delineation of the apparatus 10, including its use andoperation, demonstrate the industrial applicability of this invention.

Accordingly, it should be apparent that further numerous structuralmodifications and adaptations may be resorted to without departing fromthe scope and fair meaning of the present invention as set forthhereinabove and as described herein below by the claims.

We claim: 1- An automated positive pressure solid phase extractionapparatus, said apparatus comprising: a lifting and lowering assemblyhaving tiered lift devices disposed at a tiered loading stage forplacing tiered labware thereon and vertically moving the tiered labwarealong a vertical axis to a positive pressure manifold plate disposedvertically above said tiered loading stage; and a shuttle disposedsubstantially perpendicular to the vertical axis between said tieredloading stage under said positive pressure manifold plate and avertically accessible home stage horizontally distal from said tieredloading stage and reciprocally movable therebetween while holding thetiered labware thereon, said lifting and lowering assembly beingoperable to receive the tiered labware from said shuttle and verticallymove the tiered labware to said positive pressure manifold plate alongthe vertical axis with an operability for concurrently reciprocatingsaid shuttle. 2- An automated positive pressure solid phase extractionapparatus, said apparatus comprising: a lifting and lowering assemblyhaving a plurality of individually vertically moveable tiered liftdevices disposed at a loading stage for placing labware thereon tovertically move the labware along a vertical axis to a positive pressuremanifold plate disposed vertically above the loading stage; and ashuttle disposed substantially perpendicular to the vertical axis andhorizontally movable between the loading stage under the positivepressure manifold plate and a vertically accessible home stagehorizontally distal from the loading stage. 3- The apparatus of claim 2wherein each of said plurality of individually vertically moveabletiered lift devices comprises laterally spaced longitudinal supportmembers disposed so as to define an open shuttle receiving area. 4- Theapparatus of claim 3 further comprising a linear guide rail on whichsaid shuttle is mounted to be horizontally movable between the loadingstage under said positive pressure manifold plate and the verticallyaccessible home stage horizontally distal from the loading stage. 5- Anautomated positive pressure solid phase extraction apparatus, saidapparatus comprising: a shuttle reciprocally movable along a horizontallength of a base plate on which said shuttle is mounted; a verticallyelevated manifold plate disposed over a portion of the horizontal lengthof said base plate so as to define an elevator shaft vertically belowsaid vertically elevated manifold plate wherein said shuttle ishorizontally reciprocally movable into and out of the elevator shaft; anupper lift device disposed vertically below said vertically elevatedmanifold plate and configured to vertically reciprocally translatewithin the elevator shaft; and a lower lift device disposed verticallybelow said upper lift device and configured to vertically reciprocallytranslate within the elevator shaft below said upper lift device. 6- Theapparatus of claim 5 wherein said lower lift device comprises laterallyspaced longitudinal lower support members disposed in said elevatorshaft so as to define a lower open receiving area dimensioned to allowsaid shuttle to reciprocally move into and out of the elevator shaft. 7-The apparatus of claim 6 wherein said upper lift device compriseslaterally spaced longitudinal upper support members disposed in saidelevator shaft above said laterally spaced longitudinal lower supportmembers so as to define an upper open receiving area dimensioned toallow said shuttle to reciprocally move into and out of the elevatorshaft.